Archives of general psychiatry最新文献

Context: Smaller hippocampal volumes are well established in posttraumatic stress disorder (PTSD), but the relatively few studies of amygdala volume in PTSD have produced equivocal results.

Objective: To assess a large cohort of recent military veterans with PTSD and trauma-exposed control subjects, with sufficient power to perform a definitive assessment of the effect of PTSD on volumetric changes in the amygdala and hippocampus and of the contribution of illness duration, trauma load, and depressive symptoms.

Design: Case-controlled design with structural magnetic resonance imaging and clinical diagnostic assessments. We controlled statistically for the important potential confounds of alcohol use, depression, and medication use.

Setting: Durham Veterans Affairs Medical Center, which is located in proximity to major military bases.

Patients: Ambulatory patients (n = 200) recruited from a registry of military service members and veterans serving after September 11, 2001, including a group with current PTSD (n = 99) and a trauma-exposed comparison group without PTSD (n = 101).

Main outcome measure: Amygdala and hippocampal volumes computed from automated segmentation of high-resolution structural 3-T magnetic resonance imaging.

Results: Smaller volume was demonstrated in the PTSD group compared with the non-PTSD group for the left amygdala (P = .002), right amygdala (P = .01), and left hippocampus (P = .02) but not for the right hippocampus (P = .25). Amygdala volumes were not associated with PTSD chronicity, trauma load, or severity of depressive symptoms.

Conclusions: These results provide clear evidence of an association between a smaller amygdala volume and PTSD. The lack of correlation between trauma load or illness chronicity and amygdala volume suggests that a smaller amygdala represents a vulnerability to developing PTSD or the lack of a dose-response relationship with amygdala volume. Our results may trigger a renewed impetus for investigating structural differences in the amygdala, its genetic determinants, its environmental modulators, and the possibility that it reflects an intrinsic vulnerability to PTSD.

Context: Individuals with early onset of bipolar disorder are at high risk for suicide. Yet, no study to date has examined factors associated with prospective risk for suicide attempts among youth with bipolar disorder.

Objective: To examine past, intake, and follow-up predictors of prospectively observed suicide attempts among youth with bipolar disorder.

Design: We interviewed subjects, on average, every 9 months over a mean of 5 years using the Longitudinal Interval Follow-up Evaluation.

Setting: Outpatient and inpatient units at 3 university centers.

Participants: A total of 413 youths (mean [SD] age, 12.6 [3.3] years) who received a diagnosis of bipolar I disorder (n=244), bipolar II disorder (n=28), or bipolar disorder not otherwise specified (n=141).

Main outcome measures: Suicide attempt over prospective follow-up and past, intake, and follow-up predictors of suicide attempts.

Results: Of the 413 youths with bipolar disorder, 76 (18%) made at least 1 suicide attempt within 5 years of study intake; of these, 31 (8% of the entire sample and 41% of attempters) made multiple attempts. Girls had higher rates of attempts than did boys, but rates were similar for bipolar subtypes. The most potent past and intake predictors of prospectively examined suicide attempts included severity of depressive episode at study intake and family history of depression. Follow-up data were aggregated over 8-week intervals; greater number of weeks spent with threshold depression, substance use disorder, and mixed mood symptoms and greater number of weeks spent receiving outpatient psychosocial services in the preceding 8-week period predicted greater likelihood of a suicide attempt.

Conclusions: Early-onset bipolar disorder is associated with high rates of suicide attempts. Factors such as intake depressive severity and family history of depression should be considered in the assessment of suicide risk among youth with bipolar disorder. Persistent depression, mixed presentations, and active substance use disorder signal imminent risk for suicidal behavior in this population.

Context: Epidemiologic studies of adults show that DSM-IV intermittent explosive disorder (IED) is a highly prevalent and seriously impairing disorder. Although retrospective reports in these studies suggest that IED typically begins in childhood, no previous epidemiologic research has directly examined the prevalence or correlates of IED among youth.

Objective: To present epidemiologic data on the prevalence and correlates of IED among US adolescents in the National Comorbidity Survey Replication Adolescent Supplement.

Design: United States survey of adolescent (age, 13-17 years) DSM-IV anxiety, mood, behavior, and substance disorders.

Setting: Dual-frame household-school samples.

Participants: A total of 6483 adolescents (interviews) and parents (questionnaires).

Main outcome measures: The DSM-IV disorders were assessed with the World Health Organization Composite International Diagnostic Interview (CIDI).

Results: Nearly two-thirds of adolescents (63.3%) reported lifetime anger attacks that involved destroying property, threatening violence, or engaging in violence. Of these, 7.8% met DSM-IV/CIDI criteria for lifetime IED. Intermittent explosive disorder had an early age at onset (mean age, 12.0 years) and was highly persistent, as indicated by 80.1% of lifetime cases (6.2% of all respondents) meeting 12-month criteria for IED. Injuries related to IED requiring medical attention reportedly occurred 52.5 times per 100 lifetime cases. In addition, IED was significantly comorbid with a wide range of DSMIV/CIDI mood, anxiety, and substance disorders, with 63.9% of lifetime cases meeting criteria for another such disorder. Although more than one-third (37.8%) of adolescents with 12-month IED received treatment for emotional problems in the year before the interview, only 6.5% of respondents with 12-month IED were treated specifically for anger.

Conclusions: Intermittent explosive disorder is a highly prevalent, persistent, and seriously impairing adolescent mental disorder that is both understudied and undertreated. Research is needed to uncover risk and protective factors for the disorder, develop strategies for screening and early detection, and identify effective treatments.

Context: Two studies based on clinical samples have found an association between Toxoplasma gondii infection and history of suicide attempt. To our knowledge, these findings have never been replicated in a prospective cohort study.

Objective: To examine whether T gondii–infected mothers have an increased risk of self-directed violence, violent suicide attempts, and suicide and whether the risk depends on the level of T gondii IgG antibodies.

Design: Register-based prospective cohort study. Women were followed up from the date of delivery, 1992 to 1995 until 2006.

Setting: Denmark.

Participants: A cohort of 45 788 women born in Denmark whose level of Toxoplasma-specific IgG antibodies was measured in connection with child birth between 1992 and 1995.

Main outcome measures: Incidence rates of self-directed violence, violent suicide attempts, and suicide in relation to T gondii seropositivity and serointensity.

Results: T gondii–infected mothers had a relative risk of self-directed violence of 1.53 (95% CI, 1.27-1.85) compared with noninfected mothers, and the risk seemed to increase with increasing IgG antibody level. For violent suicide attempts, the relative risk was 1.81 (95% CI, 1.13-2.84) and for suicide, 2.05 (95% CI, 0.78-5.20). A similar association was found for repetition of self-directed violence, with a relative risk of 1.54 (95% CI, 0.98-2.39).

Conclusion: Women with a T gondii infection have an increased risk of self-directed violence.

Context: Previous epidemiological, animal, and human cognitive neuroscience research suggests that maternal smoking during pregnancy (SDP) causes increased risk of substance use/problems in offspring.

Objective: To determine the extent to which the association between SDP and offspring substance use/problems depends on confounded familial background factors by using a quasi-experimental design.

Design: We used 2 separate samples from the United States and Sweden. The analyses prospectively predicted multiple indices of substance use and problems while controlling for statistical covariates and comparing differentially exposed siblings to minimize confounding.

Setting: Offspring of a representative sample of women in the United States (sample 1) and the total Swedish population born during the period from January 1, 1983, to December 31, 1995 (sample 2).

Patients or other participants: Adolescent offspring of the women in the National Longitudinal Survey of Youth 1979 (n = 6904) and all offspring born in Sweden during the 13-year period (n = 1,187,360).

Main outcome measures: Self-reported adolescent alcohol, cigarette, and marijuana use and early onset (before 14 years of age) of each substance (sample 1) and substance-related convictions and hospitalizations for an alcohol- or other drug-related problem (sample 2).

Results: The same pattern emerged for each index of substance use/problems across the 2 samples. At the population level, maternal SDP predicted every measure of offspring substance use/problems in both samples, ranging from adolescent alcohol use (hazard ratio [HR](moderate), 1.32 [95% CI, 1.22-1.43]; HR(high), 1.33 [1.17-1.53]) to a narcotics-related conviction (HR(moderate), 2.23 [2.14-2.31]; HR(high), 2.97 [2.86-3.09]). When comparing differentially exposed siblings to minimize genetic and environmental confounds, however, the association between SDP and each measure of substance use/problems was minimal and not statistically significant.

Conclusions: The association between maternal SDP and offspring substance use/problems is likely due to familial background factors, not a causal influence, because siblings have similar rates of substance use and problems regardless of their specific exposure to SDP.

Context: The identification of modifiable predeployment vulnerability factors that increase the risk of combat stress reactions among soldiers once deployed to a war zone offers significant potential for the prevention of posttraumatic stress disorder (PTSD) and other combat-related stress disorders. Adults with anxiety disorders display heightened emotional reactivity to a single inhalation of 35% carbon dioxide (CO(2)); however, data investigating prospective linkages between emotional reactivity to CO(2) and susceptibility to war-zone stress reactions are lacking.

Objective: To investigate the association of soldiers' predeployment emotional reactivity to 35% CO(2) challenge with several indices of subsequent war-zone stress symptoms assessed monthly while deployed in Iraq.

Design, setting, and participants: Prospective cohort study of 158 soldiers with no history of deployment to a war zone were recruited from the Texas Combat Stress Risk Study between April 2, 2007, and August 28, 2009.

Main outcome measures: Multilevel regression models were used to investigate the association between emotional reactivity to 35% CO(2) challenge (assessed before deployment) and soldiers' reported symptoms of general anxiety/stress, PTSD, and depression while deployed to Iraq.

Results: Growth curves of PTSD, depression, and general anxiety/stress symptoms showed a significant curvilinear relationship during the 16-month deployment period. War-zone stressors reported in theater were associated with symptoms of general anxiety/stress, PTSD, and depression. Consistent with the prediction, soldiers' emotional reactivity to a single inhalation of 35% CO(2)-enriched air before deployment significantly potentiated the effects of war-zone stressors on the subsequent development of PTSD symptoms and general anxiety/stress symptoms but not on the development of depression, even after accounting for the effects of trait anxiety and the presence of past or current Axis I mental disorders.

Conclusion: Soldiers' emotional reactivity to a 35% CO(2) challenge may serve as a vulnerability factor for increasing soldiers' risk for PTSD and general anxiety/stress symptoms in response to war-zone stressors.